Modified CDKN2B (p15) and CDKN2A (p16) DNA methylation profiles in urban pesticide applicators

  • José Francisco Herrera-Moreno
  • Irma Martha Medina-Díaz
  • Yael Yvette Bernal-Hernández
  • Kenneth S. Ramos
  • Isabel Alvarado-Cruz
  • Betzabet Quintanilla-Vega
  • Cyndia Azucena González-Arias
  • Briscia Socorro Barrón-Vivanco
  • Aurora Elizabeth Rojas-GarcíaEmail author
Research Article


Gene-specific changes in DNA methylation by pesticides in occupationally exposed populations have not been studied extensively. Of particular concern are changes in the methylation profile of tumor-suppressor, such as CDKN2B and CDKN2A, genes involved in oncogenesis. The aim of this study was to evaluate the methylation profiles of CDKN2B and CDKN2A genes in urban pesticide applicators and their relationship with occupational exposure to pesticides. A cross-sectional study was conducted in 186 urban pesticide applicators (categorized as high or moderate exposures) and 102 participants without documented occupational exposures to pesticides. Acute and chronic pesticide exposures were evaluated by direct measurement of urinary dialkylphosphates, organophosphate metabolites, and a structured questionnaire, respectively. Anthropometric characteristics, diet, clinical histories, and other variables were estimated through a validated self-reported survey. DNA methylation was determined by pyrosequencing of bisulfite-treated DNA. Decreased DNA methylation of the CDKN2B gene was observed in pesticide-exposed groups compared to the non-exposed group. In addition, increased methylation of the CDKN2A promoter was observed in the moderate-exposure group compared to the non-exposed group. Bivariate analysis showed an association between CDKN2B methylation and pesticide exposure, general characteristics, smoking status, and micronutrients, while changes in CDKN2A methylation were associated with pesticide exposure, sex, educational level, body mass index, smoking status, supplement intake, clinical parameters, and caffeine consumption. These data suggest that pesticide exposure modifies the methylation pattern of CDKN2B and CDKN2A genes and raise important questions about the role that these changes may play in the regulation of cell cycle activities, senescence, and aging.


Pesticides Gene-specific methylation CDKN2B CDKN2A 



We are grateful to all the workers who participated in the study. The authors also thank Dr. Leticia Yáñez-Estrada and her team at the Autonomous University of San Luis Potosí, Mexico, for measurements of DAP.

Funding sources

This work was supported by CONACyT (Grant #233803).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest to report.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • José Francisco Herrera-Moreno
    • 1
    • 2
  • Irma Martha Medina-Díaz
    • 1
  • Yael Yvette Bernal-Hernández
    • 1
  • Kenneth S. Ramos
    • 3
  • Isabel Alvarado-Cruz
    • 4
  • Betzabet Quintanilla-Vega
    • 4
  • Cyndia Azucena González-Arias
    • 1
  • Briscia Socorro Barrón-Vivanco
    • 1
  • Aurora Elizabeth Rojas-García
    • 1
    Email author
  1. 1.Laboratorio de Contaminación y Toxicología Ambiental, Secretaría de Investigación y PosgradoUniversidad Autónoma de NayaritTepicMexico
  2. 2.Posgrado en Ciencias Biológico AgropecuariasUnidad Académica de AgriculturaXaliscoMexico
  3. 3.Department of Medicine, Division of Clinical Support and Data AnalyticsUniversity of Arizona College of Medicine—PhoenixPhoenixUSA
  4. 4.Departamento de ToxicologíaCentro de Investigación y de Estudios Avanzados del IPNCiudad de MéxicoMexico

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